Effects of Green-MED Diet Via the Gut-fat-brain Axis

Abdominal Obesity Metabolic Syndrome Clinical Trial

— DIRECT-PLUS  

Official title:

Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03020186
• Other study ID #: BGU
• Status: Completed
• Phase: N/A
• Start date: January 2017
• Est. completion date: March 2019

Study information

• Verified date: January 2017
• Source: Ben-Gurion University of the Negev
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat (green-MED diet) may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase.

Description:

The investigators aim to compare the effect of green-MED diet+ physical activity (PA) vs. MED diet+ PA vs. PA on the gut-fat-brain axis and to explore the additional contribution of autologous fecal microbiota derived at the rapid weight loss phase on regain phase. Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase. The investigators will follow the participants with magnetic resonance imaging (MRI) that will include abdominal and hepatic fat, cardiac and anatomic/functional brain assessments. The investigators will perform cognitive tests and will measure changes in gut microbiota and sub-metabolomic profiling. The trial will be performed in an isolated workplace (the Nuclear Research Center) which holds an exclusive cafeteria that provides free, dietary -monitored, lunch, and an internal medical department. The exclusive nutritional profile of walnuts, with its relative high polyphenols content and unique composition, may benefit several health outcomes. Epidemiologic studies and RCTs suggest that walnuts consumption is associated with better weight status, adiposity measures and cardiometabolic state. However, some individuals avoid walnuts because they are calorie-dense, and fear that they will promote weight gain. Walnuts contain numerous well-characterized beneficial nutritional components, such as unsaturated fats, especially omega-3 fatty acids, dietary fibers, and high levels of vitamins and minerals. Among other well-recognized components, nuts are highly rich in polyphenols, mainly flavonoids. Polyphenols may potentially interact with physical activity and promote neurogenesis; a process that may significantly contribute to the brain's ageing process. Similarly, the polyphenol epigallocatechin-3-gallate (EGCG, a type of catechin found in green tea), was proposed to exert neuroprotective effects. New specific developed strain of duckweed [Wolffia globose, "Mankai"] , an aquatic plant, which might serve as a protein source and contains all the 9 essential and the 6 conditional amino acids. "Mankai" [(Generally recognized as safe (GRAS)] is a cultivated strain of Wolffia globosa, which is an aquatic plant, part of the family of plants known commonly as duckweeds. Duckweeds are very simple flowering aquatic plants, which float on or just beneath the surface of still or slow-moving bodies of water. There is a long history of the use of Wolffia species, in particular Wolffia Globosa, as food, especially in Southeast Asia: Burma, Laos and northern Thailand, where it has been used as a vegetable for many generations. The nutritional composition of "Mankai" has been determined and found to be high in protein, containing all the essential and conditionally essential amino acids, dietary fibers and several vitamins and minerals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

age >30 years with abdominal adiposity (waist circumference: men > 102 cm, women > 88 cm) or dyslipidemia (TG>150mg/dl and HDL-c <40mg/dL for men and <50mg/dL for women)

Exclusion Criteria:

Individuals who may not be able to partake in PA in the gym; TGs>400 mg/dL; serum creatinine>2 mg/dL; disturbed liver function; major illness that might require hospitalization; pregnant or lactating women; presence of active cancer, is receiving or received chemotherapy in the last three years; participation in another trial; participants who are treated with Coumadin (warfarin) - given its interaction with vitamin K and high level of this vitamin in "Mankai" green shake; pacemaker or platinum implant, because of the impossibility of MRI screening.

Related Conditions & MeSH terms

• Abdominal Obesity Metabolic Syndrome
• Metabolic Syndrome
• Obesity, Abdominal

Intervention

Other:
• Physical activity

• Physical activity+ MED diet

• Physical activity+green MED diet
****Sub-study from all 3 main arms: Autologous fecal microbiota supplement intervention derived from the time of maximal weight loss: At the 6-month time period, the time of anticipated greatest weight reduction, participants's feces samples will be processed to capsulized inocula. Samples will be frozen within 2 hours and will be kept at -80c pending analysis. Participants will be randomized to receive either research capsules or identical placebo capsules between 8 and 14 months time period. Placebo capsules will consist of a combination of powdered cocoa and vegetable gelatin in normal saline/glycerol and will be identical in appearance to research capsules.

Locations

Country	Name	City	State
Israel	Nuclear research center Negev	Dimona

Sponsors (3)

Lead Sponsor	Collaborator
Ben-Gurion University of the Negev	Harvard School of Public Health, University of Leipzig

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Abdominal fat	Changes in visceral fat (MRI)	18 months
Primary	Hepatic fat	Changes in hepatic fat (MRI)	18 months
Primary	Obesity	Changes in body weight and waist circumference	6, 14, 18 months
Secondary	Brain anatomy	Changes in hippocampus volume, diffusion Tensor Imaging (MRI)	18 months
Secondary	Cognitive function-MRI	Changes in resting state connectivity (MRI, sub-study)	18 months
Secondary	Cognitive function	cognitive tests	18 months
Secondary	Cardiac state	Changes in cardiac anatomy (MRI, substudy)	18 months
Secondary	Cardiac state	Changes in cardiac function (MRI, substudy)	18 months
Secondary	Endothelial dysfunction	Changes endothelial function (ECG)	18 months
Secondary	Lipid profile	Changes in lipid biomarkers (blood draw)	6 , 14 and 18 months
Secondary	Glycemic control	Changes in glycemic biomarkers (blood draw)	6 , 14 and 18 months
Secondary	Inflammatory state	Changes in inflammatory biomarkers (blood draw)	6 , 14 and 18 months
Secondary	Metabolomic	Changes in sub-lipids (blood draw)	18 months
Secondary	Metabolomic	Changes in sub-proteins ( blood draw)	18 months
Secondary	Liver function (blood biomarkers)	Changes in liver function biomarkers (blood draw)	6 and 18 months
Secondary	Genetic signature	SNPs associated with fat distribution and visceral fat	baseline
Secondary	Epigenetics	changes in mRNAs	18 months
Secondary	Epigenetics	changes in genes' methylation	18 months
Secondary	Well being	assessed by questionnaire	18 months
Secondary	Fecal microbiota profile	Diversity Index as a key measure	6, 14, 18 months
Secondary	24h- continuous glucose levels	24h dynamics of glucose using continuous glucose monitor. substudy	2 weeks